DESCRIPTION: The goal of these studies is to characterize the role played by HIV and SIV co-receptors in virus entry, and the impact that this has on viral transmission and disease progression. In the first specific aim, proven techniques will be used to identify new co-receptors from lymphoid and non-lymphoid tissue and to characterize what strains of HIV and SIV are able to use these receptors. The second specific aim is to identify why CCR5 is non-functional for entry when expressed on murine T-cells, despite functioning when expressed on murine fibroblasts. The third specific aim is to determine why mutant HUT78 cells that express CD4 and CXCR4 are non-permissive for HIV entry or env-mediated membrane fusion. The fourth specific aim is to characterize regions of CD4 that interact with CCR5 and that are involved in the HIV entry process.